Embryonic Arsenic Exposure Triggers Long-Term Behavioral Impairment with Metabolite Alterations in Zebrafish

Area of Science:

• Environmental Toxicology
• Developmental Biology
• Neuroscience

Background:

• Arsenic trioxide (As₂O₃) is an environmental toxin with poorly understood long-term effects on developing organisms.
• Understanding the mechanisms of arsenic toxicity is crucial for assessing environmental risks.

Purpose of the Study:

• To investigate the long-term adverse effects of arsenic trioxide (As₂O₃) exposure on zebrafish development and behavior.
• To elucidate the underlying molecular and metabolic mechanisms of arsenic-induced neurotoxicity.

Main Methods:

• Zebrafish embryos were exposed to varying concentrations of As₂O₃ from gastrulation to hatching.
• Behavioral assays (motor function, anxiety, color preference) were conducted at different developmental stages (larval, adult).
• Transcriptional regulation and lipid metabolism were analyzed in exposed zebrafish.

Main Results:

• As₂O₃ exposure led to dose-dependent mortality and reduced heart rate and tail-coiling in larvae.
• Surviving larvae exhibited motor deficits and impaired color preference, persisting into adulthood.
• Locomotor function, directional and color preference were altered in adult zebrafish, linked to changes in adsl, shank3a, and tsc1b gene expression.
• Metabolic alterations, particularly in lipids like arachidonic acid and docosahexaenoic acid, were observed post-hatching.

Conclusions:

• Arsenic trioxide (As₂O₃) exposure induces significant long-term neurodevelopmental and behavioral impairments in zebrafish.
• Metabolic dysregulation, especially in lipid pathways, and altered gene expression are key mechanisms underlying arsenic toxicity.
• Findings offer insights into arsenic's impact on learning and behavior, aiding environmental risk assessment for toxins.